NEW YORK (Reuters Health) - A new study reconfirms something often forgotten by women and sometimes even by doctors: just because breast cancer has not struck a family before does not mean family members are safe from the disease.

Researchers tracking more than 6,000 women for up to six years found that most cases of breast cancer occurred in those without a family history of the disease, although many of the women had other known risk factors that can help predict an individual woman's likelihood of developing the disease.

Breast cancer accounts for about a quarter of all cancers in women, with nearly 200,000 new cases of invasive breast cancer -- disease that has spread beyond the milk ducts or milk-making glands -- diagnosed in the U.S. every year.

"I have newly-diagnosed breast cancer patients ask me all the time how they could have developed the disease since they did not have a family history," researcher Dr. Lawrence Wickerham of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Allegheny Center, in Pittsburgh, told Reuters Health in an e-mail.

Prior studies have shown that more than 70 percent of primary care doctors ask women about their family histories, while less than half collect information on other known risk factors such as whether a woman's period began before age 12 - which raises risk - or whether she has given birth, which lowers risk.

Wickerham, along with lead researcher Angelina Sontag, of Eli Lilly and Company, and their colleagues analyzed the roles of various risk factors among 6,322 postmenopausal women who had participated in two large trials of osteoporosis medications. (Eli Lilly and Company, a maker of breast cancer treatments, also funded the current study.)

At the time of each trial, all of the women were under 86 years old and none had received a previous diagnosis of breast cancer.

The team used the Breast Cancer Risk Assessment Tool (http://www.cancer.gov/bcrisktool), an online questionnaire developed by NSABP and the National Cancer Institute, to go back in time and predict the odds that the women would develop invasive disease over the next five years.

The risk calculator incorporates age of first menstruation, current age, ethnicity, reproductive history, prior breast biopsies and family history. Its score, on a scale of zero to eight, represents a woman's five-year risk as a percentage.

Some 600 women in the study group -- approximately one in ten -- had a family history of breast cancer and nearly all of these met the predictive tool's definition of high risk: a score of 1.66 percent or above.

More than half of the remaining women without family histories of breast cancer also fit into the high-risk category, however.

A total of 92 women, or 1.5 percent of the study population, went on to develop invasive breast cancer over an average follow-up period of 4 to 6 years. As expected, the actual rate of breast cancers increased with the predicted risks, as well as in the presence of a family history.

Nevertheless, more of the total number of breast cancer cases ended up being reported in women with predictions below the high-risk cut-off or without a family history.

Close to half (40) of the women who developed the disease received a risk score below 1.66 percent, for example, and nearly two of every three (60) diagnosed women had been assigned risks between 1 and 2 percent and had no family history of breast cancer.

"The single largest risk factor for developing a breast cancer is being a woman and the second largest is being a women over 50," said Wickerham. "However, there are some women who are at greater than average risk, particularly those with a family history."

The most common known risk factors found in the study population were being at least 65 years old and beginning menstruation before the age of 12, report the researchers in the journal Menopause.

"Physicians and other health care providers should consider using methods beyond asking about family history to access breast cancer risk," added Wickerham, alluding to the Breast Cancer Risk Assessment Tool. "Such efforts can help better identify women at increased risk and can better focus screening and prevention strategies for them."

By Robert PreidtMonday, December 27, 2010 HealthDay LogoHealthDay news image

Related MedlinePlus Pages

* Birth Control * Diabetes

MONDAY, Dec. 27 (HealthDay News) -- Injectable and oral birth control do not significantly affect a woman's fasting glucose and insulin levels, according to a new research.

The three-year study is the largest to measure fasting glucose and insulin levels among women using oral (desogestrel), injectable (DMPA), and non-hormonal (bilateral tubal ligation, condom, or abstinence) methods, said the researchers at the University of Texas Medical Branch in Galveston.

They found that women using DMPA experienced slight increases in glucose and insulin levels. Their glucose levels increased steadily during the first 30 months of using DMPA, with the greatest increase occurring during the first six months. These increases, however, were not large enough to cause concern, according to the researchers.

The study appears in the January issue of the journal Obstetrics and Gynecology.

"Previous studies were limited in scope and offered conflicting results, which led physicians to question whether hormonal contraception could lead to diabetes," lead author Dr. Abbey Berenson, professor, Department of Obstetrics and Gynecology and director of the Center for Interdisciplinary Research in Women's Health, said in a UTMB Health news release.

"Further studies are needed to determine how women with diabetes are affected by DMPA and oral contraception, but these results are reassuring for non-diabetic women already receiving the shot or on the pill," she added.

CANCER ADVANCES IN FOCUS: Brain and Other Central Nervous System
Yesterday

* In 1975, the annual incidence of brain and other central nervous system (CNS) cancers, including cancers of the spinal cord, among adults in the United States was 5.9 new cases diagnosed for every 100,000 persons. The incidence of these cancers among children aged 19 years or younger was 2.1 new cases per 100,000 persons.

* In the same year, the annual mortality from brain and other CNS cancers among adults was 4.1 deaths per 100,000 persons; among children aged 19 years or younger, it was 0.9 deaths per 100,000 persons.

* Magnetic resonance imaging (MRI), which facilitates diagnosis as well as treatment of brain and other CNS tumors with surgery and radiation therapy, first became widely available in the 1980s.

* Clinical trials in the 1970s and 1980s showed that adding radiation therapy to surgery prolonged the survival of patients with glioma, a type of brain tumor that accounts for approximately 70% of the malignant primary brain tumors diagnosed in adults in the United States each year.

* Chemotherapy was not a standard treatment for brain tumors because most early chemotherapy drugs could not cross the blood-brain barrier. One class of drugs, the nitrosoureas, was found to cross the blood-brain barrier and was shown in clinical trials to produce a small but clear improvement in the length of patient survival when combined with surgery and radiation therapy.

Today

* In 2007, the latest year for which we have updated statistics, the U.S. incidence rate of brain and other CNS cancers among adults was 6.4 new cases per 100,000 persons; among children aged 19 years or younger, it was 2.9 new cases per 100,000 persons. The higher incidence rates observed today are likely due, in part, to an improved ability to diagnose brain and other CNS tumors with advanced imaging technologies.

* MRI is now an accepted standard technology for imaging brain and other CNS tumors. A newer technology called functional MRI, which measures changes in blood flow that accompany brain activity, can be helpful in determining how well brain regions are working, in assessing potential risk from surgery, and in planning treatment. New intraoperative MRI machines can be used to monitor the extent of tumor removal during surgery.

* The orally administered drug temozolomide, which first became available in the United States in 1999, can prolong the survival of patients with glioma when combined with radiation therapy. High-dose chemotherapy regimens for the treatment of some types of childhood brain tumor can delay the need for radiation therapy, possibly reducing harm to the developing brain.

* Antiangiogenesis agents—drugs that block the growth of new blood vessels to tumors—have shown some promise in the treatment of gliomas. Gliomas are highly vascularized tumors, meaning they have a large number of blood vessels. Drugs that block the development of these blood vessels are being tested in clinical trials of patients with brain tumors. Based on the promising results of two clinical trials, one of which was conducted at the National Institutes of Health (NIH), the Food and Drug Administration gave accelerated approval in May 2009 to the antiangiogenesis agent bevacizumab (Avastin®) for the treatment of recurrent glioblastoma, which is the most common form of glioma. Two phase III clinical trials, including one supported by NIH, are testing the drug in newly diagnosed patients.

* Researchers are exploring the use of other novel approaches, such as targeted therapy, gene therapy, immunotherapy, and vaccine therapy, for the treatment of brain and other CNS cancers.

* A new scale developed by NIH, which is based on tumor size, tumor location, and a patient’s ability to perform everyday tasks, can help surgeons identify which patients with glioblastoma will benefit from additional surgery when their tumor recurs.

* Scientists are beginning to understand the genetic complexity of brain tumors, which will facilitate the design of more effective treatments. An understanding of the genetic changes that drive the growth of brain tumors will allow researchers to choose the best candidate targeted drugs for testing in clinical trials.

* In 2008, The Cancer Genome Atlas (TCGA) project reported the first results of its large-scale, comprehensive study of gene changes in glioblastoma (a type of glioma). These results identified three previously unrecognized mutations that occur frequently in glioblastoma and three cell-signaling pathways that may help drive tumor growth. The results also shed new light on molecular mechanisms that may make tumors resistant to some chemotherapy drugs. In 2010, additional results from TCGA showed that glioblastoma comprises four different molecular subtypes that have different responses to chemotherapy and radiation therapy.

* The Glioma Molecular Diagnostic Initiative has already made extensive genetic and related clinical data from more than 800 glioma patients available to researchers worldwide in a public data repository and bioinformatics work space known as REMBRANDT.

* Despite tremendous advances in our understanding of brain cancer biology, substantial progress in brain tumor diagnosis and treatment, and marked improvements in the quality of life of brain tumor patients, the mortality rate for brain and other CNS cancers has remained largely unchanged over the past 30 to 40 years.

Tomorrow

* We will continue to explore the use of new imaging technologies in the diagnosis, treatment, and follow-up care of brain and other CNS cancers. For example, magnetic resonance perfusion imaging is a technology that enables measurement of the volume of blood flowing through the brain. This information will allow better estimates of tumor grade, size, and location before surgery and permit recurrent tumor tissue to be distinguished from damage to brain tissue caused by radiation therapy, thereby reducing the need for follow-up surgical biopsies. In addition, imaging technologies such as positron emission tomography, single photon emission computed tomography, and diffusion-weighted MRI can help measure tumor metabolic activity, tumor cell proliferation, and the amount of oxygen that reaches tumor cells.

* We will refine methods of delivering chemotherapy drugs and other agents to the brain and CNS, including the development of drugs that have the ability to penetrate the blood-brain barrier. Other delivery techniques, such as convection-enhanced delivery, in which drugs or other anticancer agents are delivered under pressure (convection) through a catheter inserted directly into or near a tumor, may prove valuable.

* We will continue to explore the potential of new antiangiogenesis agents in controlling tumor growth.

* Intensive research into the genetic changes that lead to the formation of brain and other CNS cancers, through TCGA and other collaborative projects, will yield new opportunities for developing therapies that target these changes.

* We will expand our understanding of the role that tumor stem cells play in the formation of brain and other CNS tumors and their resistance to treatment and will use that knowledge to develop new therapies that target tumor stem cell-signaling pathways. First discovered in 2003, brain tumor stem cells make up only a small proportion of the cells in human brain tumors, but they may drive tumor growth and metastasis and contribute to resistance to treatment.Cancer Advances in Focus: Brain and Other Central Nervous System - National Cancer Institute

Adapted from the NCI Cancer Bulletin, vol. 7/no. 24, December 14, 2010 (see the current issue).

Regular sunscreen use may reduce the risk of developing melanoma, according to results of a randomized controlled trial that were reported December 6, 2010, in the Journal of Clinical Oncology. The trial is the first prospective, randomized study to investigate the link between sunscreen use and melanoma, the most deadly type of skin cancer.

Researchers led by Adèle Green, Ph.D., of the Queensland Institute of Medical Research examined the incidence of melanoma among 1,621 white adults in a township in Queensland, Australia. They divided the study participants, age 20 to 69, into two groups. From 1992 to 1996, the participants in one group were given an unlimited supply of a broad-spectrum sunscreen with a sun protection factor (SPF) of 16 and were asked to apply it every morning to their head, neck, arms, and hands, and reapply it after heavy sweating, bathing, or long sun exposure. The control group continued using sunscreen of any SPF at their usual discretionary frequency, which for some included no use.

Dr. Green and her colleagues followed the study participants for 10 additional years and tracked all cases of primary melanoma newly diagnosed between 1993 and 2006. They found 11 new cases of melanoma in the daily sunscreen group compared with 22 cases in the discretionary sunscreen group, a 50 percent reduction. Invasive melanoma was reduced by 73 percent in the daily sunscreen group compared with the control group (3 versus 11 cases).

The authors noted that their results are of borderline statistical significance and suggested that their findings for invasive melanoma in particular “should be interpreted cautiously.” Nevertheless, they concluded, “among adults age 25 to 75 years, regular application of SPF 15+ sunscreen in a 5-year period appeared to reduce the incidence of new primary melanomas for up to 10 years.”

In an accompanying editorial, Phyllis Gimotty, Ph.D., and Karen Glanz, Ph.D., of the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania School of Medicine wrote: “To our knowledge, the trial’s findings are the first to provide strong evidence for a reduction in the incidence of invasive melanoma after regular application of broad-spectrum sunscreen in adults…. It is unlikely that another trial of comparable scope and rigor will be conducted in the foreseeable future.”

Furthermore, they wrote, although “the question of its efficacy with respect to melanoma prevention should no longer deter scientists or clinicians from recommending sunscreen use,” effective skin cancer prevention should also include avoiding exposure to ultraviolet rays, using clothing to shield skin from the sun, and performing regular skin self examinations.
“This study provides important evidence regarding the role of sunscreen use as part of a range of sun-protective behaviors that effectively reduce risk of melanoma,” commented Margaret Tucker, M.D., of NCI’s Division of Cancer Epidemiology and GeneticsRegular Sunscreen Use May Reduce Invasive Melanoma Risk - National Cancer Institute

Zoledronic Acid Did Not Improve Disease-Free Survival in Breast Cancer

Adapted from the NCI Cancer Bulletin, vol. 7/no. 24, December 14, 2010 (see the current issue).

The addition of zoledronic acid, a bisphosphonate, to standard adjuvant therapy for women with stage II or III breast cancer did not extend disease-free survival (DFS), according to results from the phase III AZURE trial presented December 9, 2010, at the San Antonio Breast Cancer Symposium (SABCS). The findings run counter to those from an earlier trial, ABCSG-12, which showed improved DFS in premenopausal women with early-stage breast cancer who received zoledronic acid in addition to hormone therapy.

It is important to note, said Robert Coleman, M.D., the AZURE trial’s principal investigator, that the patient populations in the two trials were very different. AZURE enrolled both premenopausal and postmenopausal women; ABCSG-12 enrolled only premenopausal women who, as part of the trial, received the drug goserelin to induce early menopause.

The AZURE investigators enrolled 3,360 women at 174 treatment centers in the United Kingdom. The women were randomly assigned to receive either standard adjuvant treatment—chemotherapy, hormone therapy, or both, chosen by their treating physician—or to standard adjuvant treatment plus 5 years of zoledronic acid.

After almost 5 years of follow-up, no difference in DFS or overall survival (OS) was observed between the groups. However, in a preplanned subset analysis, women who had been menopausal for at least 5 years had significantly increased DFS and OS with the addition of zoledronic acid to standard treatment. Premenopausal women experienced no benefit from the addition of the bisphosphonate in the subset analysis. The updated results from ABCSG-12 presented at SABCS continued to show a statistically significant improvement in DFS and a trend toward improved OS in women who received zoledronic acid.

“Our results are strikingly different from those observed in ABCSG-12, and we need to understand why. I don’t believe one is right and one is wrong. I think we need to understand the biology as to why we’re seeing these different outcomes,” said Dr. Coleman. “Our hypothesis would be that adjuvant bisphosphonate efficacy is dependent on a low estrogen or inhibited concentration within the bone microenvironment,” he continued.

“Based on these data, I believe the routine adjuvant use of zoledronic acid to prevent recurrence is not indicated,” said Sharon Giordano, M.D., from the University of Texas M. D. Anderson Cancer Center at the press conference. “The difference in outcome by menopausal status is very intriguing but not definitive.” She continued, “the AZURE trial will not be the final word on this topic.” Ongoing large trials testing bisphosphonates for the adjuvant treatment of breast cancer include NSABP B-34, the Gain trial, the NATAN trial, and SWOG-S0307.Zoledronic Acid Did Not Improve Disease-Free Survival in Breast - National Cancer Institute

Title 21 Code of Federal Regulations 640.120(a) - The Director, Center for Biologics Evaluation and Research, may approve an exception or alternative procedures to any requirement in subchapter F (Biologics) of Chapter I (Parts 600 - 680) of title 21 of the Code of Federal Regulations regarding blood, blood components or blood products.

Both licensed and unlicensed blood establishments must submit requests for an exception or alternative procedure to the requirements in Parts 600-680. Licensed establishments should submit the request in accordance with 21 CFR 601.12 and may reference our guidance document entitled: Guidance for Industry: Changes to an Approved Application: Biological Products: Human Blood and Blood Components Intended for Transfusion or for Further Manufacture (July 2001).

Requests for such exceptions or alternative procedures should ordinarily be made in writing, however, in limited circumstances, such requests may be made orally and permission may be given orally by the Director. Oral requests and approvals must be promptly followed by written requests and written approvals.

It should be noted that requests for exceptions or alternate procedures includes specific circumstances and may require submission of supporting data unique to the circumstance. Publication of these approvals for a specific exception or alternative procedure does not necessarily mean that they can be generally applied to other manufacturers.

Scientists at the Food and Drug Administration’s Center for Biologics Evaluation and Research developed an anthrax challenge model that was used to characterize a novel prototype dual vaccine against smallpox and anthrax developed by investigators at the National Cancer Institute. This vaccine incorporates the genes for two proteins, IL-15 and anthrax protective antigen (PA), into an existing smallpox vaccine virus. One protein (IL-15) enhances the vaccine’s anti-smallpox potency; the other protein (PA) stimulates immune responses to anthrax. This low-cost, reliable challenge model will facilitate proof-of-concept evaluations of other candidate anthrax vaccines and therapeutics.

The currently licensed smallpox vaccine, Acam2000® is highly effective; however, it is associated with serious complications, such as those affecting the heart, brain, and skin, and is not recommended for use in certain groups, such as those with severe immune deficiency. This was also true of the previously licensed smallpox vaccine, Dryvax®.

(ACAM2000, (Smallpox (Vaccinia) Vaccine, Live). The currently licensed anthrax vaccine must be administered multiple times over a long period in order to provide protection (BIOTHRAX (Anthrax Vaccine Adsorbed).

Researchers in the Center for Biologics Evaluation and Research and the Centers for Disease Control and Prevention developed a "universal," off-the-shelf vaccine designed to reduce illness and slow the spread of disease caused by new influenza A viruses that emerge suddenly, spread quickly, and for which there is no specific vaccine available. A single dose of the vaccine reduced illness and virus levels in mice later infected with highly virulent (disease-causing) H1N1 and H3N2 (seasonal influenza), and H5N1 (bird flu).

The key to the new vaccine's broad protection is that it is designed to trigger immune responses against proteins called NP and M2--two protein targets in all influenza viruses that change over time much more slowly than the HA and NA proteins targeted by traditional vaccines. The vaccine is designed to express NP and M2 from a replication-defective form of another respiratory virus, and is administered nasally, which enables it to stimulate the immune system in the mucous membranes, where influenza viruses launch their infection.

This type of vaccine, if effective in humans, could be stockpiled and then used to reduce deaths and severe illness in the event of delayed production of traditional vaccine against a newly emergent influenza virus.